PLoS ONE (Jan 2014)

Poly(ADP-ribose) polymerase 1 (PARP1) overexpression in human breast cancer stem cells and resistance to olaparib.

  • Marine Gilabert,
  • Simon Launay,
  • Christophe Ginestier,
  • François Bertucci,
  • Stéphane Audebert,
  • Mathieu Pophillat,
  • Yves Toiron,
  • Emilie Baudelet,
  • Pascal Finetti,
  • Tetsuro Noguchi,
  • Hagay Sobol,
  • Daniel Birnbaum,
  • Jean-Paul Borg,
  • Emmanuelle Charafe-Jauffret,
  • Anthony Gonçalves

DOI
https://doi.org/10.1371/journal.pone.0104302
Journal volume & issue
Vol. 9, no. 8
p. e104302

Abstract

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BACKGROUND:Breast cancer stem cells (BCSCs) have been recognized as playing a major role in various aspects of breast cancer biology. To identify specific biomarkers of BCSCs, we have performed comparative proteomics of BCSC-enriched and mature cancer cell populations from the human breast cancer cell line (BCL), BrCA-MZ-01. METHODS:ALDEFLUOR assay was used to sort BCSC-enriched (ALDH+) and mature cancer (ALDH-) cell populations. Total proteins were extracted from both fractions and subjected to 2-Dimensional Difference In-Gel Electrophoresis (2-D DIGE). Differentially-expressed spots were excised and proteins were gel-extracted, digested and identified using MALDI-TOF MS. RESULTS:2-D DIGE identified poly(ADP-ribose) polymerase 1 (PARP1) as overexpressed in ALDH+ cells from BrCA-MZ-01. This observation was confirmed by western blot and extended to four additional human BCLs. ALDH+ cells from BRCA1-mutated HCC1937, which had the highest level of PARP1 overexpression, displayed resistance to olaparib, a specific PARP1 inhibitor. CONCLUSION:An unbiased proteomic approach identified PARP1 as upregulated in ALDH+, BCSC-enriched cells from various human BCLs, which may contribute to clinical resistance to PARP inhibitors.